Persson Pontus B, Skalweit Angela, Mrowka Ralf, Thiele Bernd-Joachim
Tucholskystr. 2, 10783 Berlin, Germany.
Am J Physiol Regul Integr Comp Physiol. 2003 Sep;285(3):R491-7. doi: 10.1152/ajpregu.00101.2003.
Studies published recently have considerably enhanced our understanding of the mechanisms controlling renin production. With regard to the control of renin transcription, two enhancer regions have been identified that markedly augment renin synthesis in cell lines. In the absence of this enhancer activity, the basic promoter of the renin gene increases transcription only two- to threefold. The location of one (Jones CA, Sigmund CD, McGowan RA, Kane-Haas CM, and Gross KW. Mol Endocrinol 4: 375-383, 1990) transcription enhancer in the mouse gene is at about -2.7 kb and in humans at roughly -11 kb. A second important region has been identified in a chorionic cell line to be located approximately 5 kb upstream of the transcription start site in humans. Another potentially important regulatory region may lie within approximately 3.9 kb upstream of the -11 kb enhancer, as suggested by several conserved sequences among species in this region. In addition to the control of renin transcription, it seems that renin translation and the stability of renin mRNA are also effectively regulated. This occurs via the 3'-untranslated region, to which several proteins can bind. The binding proteins were identified as hnRNP K and E1, dynamin, nucleolin, MINT homologous protein, and Y-Box 1.
最近发表的研究极大地增进了我们对控制肾素产生机制的理解。关于肾素转录的控制，已鉴定出两个增强子区域，它们能显著增强细胞系中肾素的合成。在缺乏这种增强子活性的情况下，肾素基因的基本启动子仅能使转录增加两到三倍。小鼠基因中一个转录增强子（Jones CA、Sigmund CD、McGowan RA、Kane-Haas CM和Gross KW。《分子内分泌学》4：375 - 383，1990）的位置约在 -2.7 kb处，在人类中约在 -11 kb处。在绒毛膜细胞系中已鉴定出另一个重要区域，位于人类转录起始位点上游约5 kb处。根据该区域物种间的几个保守序列推测，另一个潜在的重要调控区域可能位于 -11 kb增强子上游约3.9 kb范围内。除了肾素转录的控制外，肾素翻译和肾素mRNA的稳定性似乎也受到有效调控。这是通过3' - 非翻译区实现的，有几种蛋白质可与之结合。这些结合蛋白被鉴定为hnRNP K和E1、发动蛋白、核仁素、MINT同源蛋白以及Y - 盒1。
